Sustained Effects of Hypertonic Saline on Mucociliary Clearance in Subjects With Chronic Bronchitis

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The purpose of this research study is to examine the effects of two weeks of daily dosing of inhaled salt water mist (hypertonic saline - HS) on actual measurements of mucociliary and cough clearance in patients with the chronic bronchitis type of Chronic Obstructive Pulmonary Disease (COPD.

Defective mucociliary clearance (MCC) is central to the development and/or worsening of several kinds of lung diseases, including COPD/chronic bronchitis (CB), cystic fibrosis (CF), and bronchiectasis. In each case, defective MCC leads to the development of lung infections and damage to the airways from ongoing inflammation caused by a person's inability to clear mucus from the lungs.

The investigators' previous studies have shown that the administration of inhaled HS (hypertonic saline) not only acutely accelerates MCC in CF, but also that repetitive use "resets" the baseline rate of MCC within 2 weeks. It is likely that the sustained effect of HS on MCC was responsible for the ~60% reduction in the frequency of pulmonary disease exacerbations, reduced antibiotic use and improved lung function in a long-term study of HS in CF volunteers. As a result, HS has now become a standard therapy for CF lung disease and its success raises optimism that similar benefits might occur in patients with CB.

In this study the investigators will use mildly radioactive particles, technetium bound to sulfur colloid, to measure and compare the sustained effects on mucus clearance of two weeks of daily dosing of 7% hypertonic saline versus a low salt control treatment for subjects with CB. We will also be collecting sputum and breath condensation to analyze for protein and inflammatory changes that might occur with exacerbations.

Our long term goals are to improve our understanding of MCC in health and disease and to develop better therapies that support and/or restore MCC in patients with these diseases to reduce lung infections.

The intervention consists of the subject receiving both concentrations of inhaled sodium chloride solution, each during a different home treatment periods. Subjects randomized to order AB will receive inhaled 7% NaCl (sodium chloride solution) mist during the first home treatment period, then 0.12% NaCL during the second home treatment period.

Other: Inhaled 7% HS (NaCl) home treatment

Administering inhaled 7% NaCl for two weeks of home treatment vs. a placebo of 0.12% NaCL during a separate home treatment period, and assessing the effects of each primarily by MCC study.

Placebo Comparator: BA: 0.12% NaCl home tx, then 7% HS

Subjects randomized to order BA will receive inhaled 0.12% NaCl mist during the first home treatment period, then Inhaled 7% HS home treatment during the second home treatment period.

Other: Inhaled 7% HS (NaCl) home treatment

Administering inhaled 7% NaCl for two weeks of home treatment vs. a placebo of 0.12% NaCL during a separate home treatment period, and assessing the effects of each primarily by MCC study.

Measure and compare the sustained effects on mucus clearance of two weeks of daily dosing of hypertonic saline versus a low salt control treatment for subjects with CB. [ Time Frame: Approximately 11 weeks ]

Using a gamma camera and inhalation of technicium bound to sulfur colloid, mucus clearance can be measured. Will do this with two different types of inhaled saline.

Secondary Outcome Measures
:

We will also be collecting sputum and breath condensation to analyze for protein and inflammatory changes that might occur with exacerbations. [ Time Frame: Within 2 years after all data collection has ended ]

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Ages Eligible for Study:

40 Years to 80 Years (Adult, Senior)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Volunteers who meet all of the following criteria will be eligible for study participation:

Age 40-80 years, inclusive

Non-pregnant subjects must be either not sexually active, post-menopausal, surgically sterilized, or agree to use an appropriate "double barrier" method (such as diaphragm and condom), or must currently be using a prescribed transdermal, injection, implant, or oral contraceptive during study participation.

Concomitant presence of congestive heart failure, active coronary syndromes, or other disease that in the opinion of the investigator would increase the risk resulting from participation

Recent change in respiratory medications, including acute antibiotic or systemic corticosteroid interventions within the last 4 weeks

History of intolerance or hypersensitivity to hypertonic saline or short acting inhaled beta agonist

Significant broncho reactivity by examination or pulmonary function testing (PFT), that in the opinion of the investigator would increase the risk of HS use

Radiation exposure within the 12 months prior to study participation that would cause them to exceed Federal Regulations by participating in this study

Subjects with a positive pregnancy test

Subjects who, in the opinion of the Principal Investigator, should not participate in the study

Subjects may be temporarily excluded from screening should they experience a respiratory tract infection that requires treatment with antibiotics and/or steroids. They may become eligible for screening four weeks after completing their treatment providing their symptoms have resolved.